Optimization criteria for ordering myeloid neoplasm next-generation sequencing

Myeloid neoplasms (MNs) frequently harbor pathogenic mutations not detected by karyotyping and fluorescence in situ hybridization; hence, next-generation sequencing (NGS) is necessary for diagnosis, risk stratification, and therapy. If, however, NGS is not clinically indicated but still performed, the results may promote futile avenues of investigation, heighten patient distress, and increase cost.

We created criteria to approve NGS testing for MN (MN-NGS) with the goal of maximizing actionable results. These actionable results include making a new MN diagnosis, characterizing a MN with baseline mutational status, and altering treatment plans. Approval criteria included clinical suspicion of new, relapsed, or worsening disease and end-of-induction chemotherapy. Cancellation criteria included the suspicion of non-myeloid disease only, no suspicion of progression of a known MN, no evidence for recurrence post-transplant, a diagnosis of chronic myeloid leukemia, and cases using blood when a concurrent bone marrow NGS is being performed. We applied these criteria to NGS tests ordered at our institution between August and December 2018 and determined whether any tests meeting our cancelation criteria yielded actionable results.

Consecutive MN-NGS orders (n = 174) were retrospectively categorized as appropriate (Group A, n = 115), inappropriate (Group B, n = 29), and appropriately canceled (group C, n = 30). Seventy-five of the 115 (65%) Group A tests and none of the 29 (0%) Group B tests yielded actionable results (p < 0.0001).

Approximately one third (59/174) of MN-NGS test orders can be safely canceled using these criteria, which would result in $150,370 of Centers for Medicare and Medicaid Services-reimbursed savings annually.